Sensor with rotatable sensor element and pressure equalization mechanism

ABSTRACT

A sensor may include a sensing element retained within a storage compartment filled with a storage medium, which may also be used as a calibration medium. The sensing element can include a sensing surface located away from the distal end of the sensing element, such that an inactive section of the sensing element can cooperate with a sealing member such as an O-ring to form part of the seal retaining the storage/calibration medium. The sensing element can be extended and retracted from the storage compartment to expose the sensing surface to a process medium, while preserving the storage medium within the storage compartment for post-measurement validation.

BACKGROUND Technical Field

Embodiments described herein relate to sensor systems and associateddevices, and in particular to sensor systems including integratedstorage and calibration compartments.

Description of the Related Art

In biopharmaceutical manufacturing processes, the use of single-usemeasurement systems pushes the responsibility of cleaning,sterilization, and validation processes to the system vendors, increasesthe speed and flexibility of the manufacturing process and reduces thecapital investment for system users who are the biopharmaceuticalmanufacturers.

With single-use systems, sensors such as pH and dissolved oxygen (DO)sensors can be integrated into a system such as a single-use bioreactorbag, or elsewhere in a process flow. The final system product can thengo through a gamma irradiation process for the sterilization of thesystem and be shipped to the end user customer. At the end user site,the pH sensors on the system are not accessible to the operator for astandard calibration process without breaching the sterility of thebioreactor bag or other structure. However, an on-site calibrationand/or validation of the sensors may nevertheless be required before amanufacturing process, such as a cell culture, begins. After themanufacturing process, an additional post-measurement validation of thesensors may also be required.

SUMMARY

In one embodiment, a sensor structure is provided, including a storagecompartment configured to retain a storage medium therein, a sensingelement extending through an aperture in the compartment and including asensing structure, a distal end of the sensing structure locatedproximal a distal end of the sensing element, the sensing elementmovable between a first position in which the sensing structure is influid communication within the storage compartment and a second positionin which the sensing structure is not in fluid communication with thestorage compartment, and a sealing element disposed at least partiallywithin the aperture and configured to engage a surface of the sensingelement to provide a seal inhibiting fluid flow in or out of storagecompartment through the aperture.

The sensing surface can be substantially flush with the adjacentsurfaces of the sensing element. The sensing element can include asection of substantially constant cross-sectional shape extendingbetween a point distal the proximal end of the sensing surface and apoint proximal the distal end of the sensing surface. The sensingsurface can form at least part of an outer surface of a cylindricalsection of the sensing element. A shape of the surface of the sensingelement in contact with the sealing element can remain substantiallyconstant during movement of the sensing element from the first positionto the second position.

The sealing element can include a gasket. The sealing element caninclude an O-ring. The sealing element can include a resilient material.The sensing element can include a pH probe. The sensing structure caninclude a glass electrode. The sensing structure can be in electricalcommunication with a reference electrode.

The storage medium can be configured to be used as a calibration mediumfor the sensing element. The storage solution can have a pH of less than6.0, less than 5.0, or less than 4.0. The storage solution can have a pHof between 0 and 14, between 1 and 13, between 3 and 12, between 4 and10.5, between 5 and 10.5, or between 6 and 10.5.

Translating the sensing element between the first position and thesecond position can, in some embodiments, not displace a substantialamount of the storage solution from the storage compartment. Translatingthe sensing element between the first position and the second positioncan, in some embodiments, not expose the interior of the storagecompartment. The translating the sensing element between the firstposition and the second position can displace less than 90% pf thestorage solution from the storage compartment, less than 50% of thestorage solution from the storage compartment, less than 10% of thestorage solution from the storage compartment, 5% of the storagesolution from the storage compartment, or less than 3% of the storagesolution from the storage compartment, or less than 1% of the storagesolution from the storage compartment.

The sensor structure can additionally include a second sensing elementextending parallel to the first sensing element, where the secondsensing element extends through a second aperture in the storagecompartment and engages with a second sealing element disposed at leastpartially within the second aperture to provide a seal inhibiting fluidflow in or out of storage compartment through the second aperture. Thestorage compartment can include a first chamber and a second chamber,the sensing element extending through both the first chamber and thesecond chamber, where the sensing structure of the sensing element iswithin the first chamber when the sensing element is in the firstposition, and where the sensing element is longitudinally translatableto a third position in which the sensing structure is located within thesecond chamber. The first chamber can retain the storage solution, andthe second chamber can retain a calibration medium, the calibrationmedium having a pH which is different from the pH of the storagesolution.

In another embodiment, a method is disclosed of measuring a property ofa process medium using a sensor system including a storage compartmentconfigured to retain a storage solution therein, and a sensing elementextending through an aperture in the compartment and including a sensingstructure, a distal end of the sensing structure located proximal adistal end of the sensing element, the sensing element longitudinallytranslatable between a first position in which the sensing structure islocated within the storage compartment and a second position in whichthe sensing structure is located outside the storage compartment, themethod including recording a first measurement when the sensing elementis in a first position in which the sensing structure of the sensingelement is positioned outside of the storage compartment and exposed tothe process medium, moving the sensing element from the first positionto a second position in which the sensing structure of the sensingelement is positioned within or otherwise exposed to the storagecompartment, and recording a second measurement when the sensing elementis in the second position. The method can additionally include, prior torecording the first measurement when the sensing element is in the firstposition recording an initial measurement when the sensing element is inan initial position in which the sensing structure of the sensingelement is positioned within the storage compartment and exposed to thestorage solution, and longitudinally translating the sensing elementfrom the initial position to the first position.

In another embodiment, a single-use bioreactor component is provided,including a process chamber configured to retain a process medium withinan interior of the chamber, a storage compartment secured relative tothe chamber, the storage compartment including an aperture extendingbetween an interior chamber of the storage compartment and the processchamber, the storage compartment including a storage and calibrationmedium within the interior chamber of the storage compartment, a sensingstructure extending through at least a portion of the storagecompartment and into the interior of the process chamber, the sensingstructure including a sensing surface exposed to the storage andcalibration medium within the storage compartment, and a sealingstructure disposed adjacent or within the aperture extending between aninterior chamber of the storage compartment and the process chamber, thesealing structure cooperating with an inactive portion of the sensingstructure to form a seal inhibiting flow of the storage and calibrationmedium through the aperture,

The interior of the process chamber and the interior chamber of thestorage chamber can form part of a sealed and sterilized portion of thesingle-use bioreactor component. The process chamber can include asingle-use bioreactor bag. The process chamber can include a fluidchannel configured to be placed in communication with a bioreactorchamber. The sensing structure can be configured to be moved between afirst position in which the sensing surface is exposed to the storageand calibration medium within the storage compartment, and a secondposition in which the sensing surface is exposed to the interior of theprocess chamber, and the sealing structure can be configured to maintainthe seal inhibiting flow of the storage and calibration medium throughthe aperture during movement of the sensing structure between the firstposition and the second position. A shape of the surface of the portionof the sensing element in contact with the sealing element can remainsubstantially constant during movement of the sensing element from thefirst position to the second position. The single-use bioreactorcomponent can additionally include at least one sterile port incommunication with the interior chamber of the storage compartment toallow access to the storage and calibration medium without compromisingthe sterility of the single-use bioreactor component.

In another embodiment, a single-use bioreactor component is provided,including a process compartment configured to retain a process mediumtherein, a storage compartment including an aperture extendingtherethrough, the storage compartment containing a calibration medium, asensing structure, where a first portion of the sensing structure is influid communication with the process compartment, and where a secondportion of the sensing structure is in fluid communication with thestorage compartment, the second portion of the sensing structureincluding a sensing surface, and a sealing structure disposed adjacentor within the aperture in the storage compartment, the sealing structurecooperating with a portion of the sensing structure to form a sealinhibiting flow of the calibration medium through the aperture.

The sensing structure can be configured to be moved between a firstposition in which the first portion of the sensing structure is in fluidcommunication with the process compartment, and a second position inwhich at least part of the second portion of the sensing structure is influid communication with the storage compartment to expose the sensingsurface to the process compartment. The sealing structure can beconfigured to maintain the seal inhibiting flow of the storage andcalibration medium through the aperture during movement of the sensingstructure between the first position and the second position. Thesensing structure can be rotated between the first position and thesecond position. The sensing structure can be translated between thefirst position and the second position. A surface profile of the portionof the sensing element in contact with the sealing element can remainsubstantially constant during movement of the sensing structure from thefirst position to the second position.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side cross-sectional view schematically illustrating anembodiment of a pH sensing element.

FIG. 2 is a side cross-sectional view schematically illustrating anembodiment of a pH sensing element including a sensing structure locatedat a point located away from the end of the structure.

FIG. 3A is a side cross-sectional view schematically illustrating anembodiment of a sensor structure including a sensing element such as thesensing element of FIG. 2 and a storage compartment containing acalibration solution.

FIG. 3B is a side cross-sectional view schematically illustrating thesensor structure of FIG. 3A, with the sensing element displaced toexpose the sensing structure.

FIG. 4A is a side cross-sectional view schematically illustrating thesensor structure of FIG. 3A, shown in a sealed position relative tomedia to be tested.

FIG. 4B is a side cross-sectional view of the sensor structure in FIG.4A, shown in an extended position in which the sensing structure of thesensing element is exposed to the media to be tested.

FIG. 5A is a side cross-sectional view schematically illustrating anembodiment of a sensor structure including a dual-chamberstorage/calibration compartment, with the sensing structure of thesensing element located in the upper chamber.

FIG. 5B is a side cross-sectional view of the sensor structure of FIG.5A, with the sensing structure of the sensing element located in thelower chamber.

FIG. 5C is a side cross-sectional view of the sensor structure of FIG.5A, with the sensing structure of the sensing element exposed to theexterior of the storage/calibration compartment.

FIG. 6 is a side cross-sectional view schematically illustrating anembodiment of a storage compartment configured to retain therein a pairof sensing elements oriented parallel to one another.

FIG. 7 is a side cross-sectional view schematically illustrating anembodiment of a sensor structure including a sensing element such as thesensing element of FIG. 2 and a storage compartment including two portsallowing access to the storage medium inside the storage compartment.

FIG. 8 is a side cross-sectional view schematically illustrating anembodiment of a sensor structure including a sensing element such as thesensing element of FIG. 2 and a storage compartment, where the storagecompartment is disposed adjacent a portion of a fluid path.

FIG. 9A is a perspective view schematically illustrating anotherembodiment of a sensing element. FIG. 9B is a side view schematicallyillustrating the sensing element of FIG. 9A.

FIG. 10A is a side view schematically illustrating an embodiment of asensor structure including the sensing element of FIG. 9A, shown in aposition in which the sensing surface is exposed to astorage/calibration medium.

FIG. 10B is a cross-sectional view of the sensor structure of FIG. 10A,taken along the line 10B-10B of FIG. 10A.

FIG. 10C is a side view of the sensor structure of FIG. 10A, with thesensing element moved to a position in which the sensing surface can beexposed to a process medium.

FIG. 11A is a side view of another embodiment of a sensor structureincluding a sensing element such as the sensing element of FIG. 2 and astorage compartment containing a calibration solution, shown insertedinto a tube port. FIG. 11B is a perspective view of the sensor structureof FIG. 11A.

FIG. 11C is a perspective view of an embodiment in which a supplementalsecurement device is used to secure the sensor structure of FIG. 11Arelative to the tube port.

FIGS. 12A and 12B are cutaway figures which illustrate the internalcomponents of the sensor structure of FIG. 11A in a retracted andextended configuration, respectively.

FIG. 13A is a side view of another embodiment of a sensor structureincluding a sensing element such as the sensing element of FIG. 2 and astorage compartment containing a storage solution, configured to beinserted into a tube port. FIG. 13B is a side view of the sensor of FIG.13A, shown in an extended position.

FIG. 14A is a cross-sectional perspective view of the sensor structureof FIG. 13A, shown in a retracted position. FIG. 14B is across-sectional perspective view of the sensor structure of FIG. 13A,shown in an extended position.

FIG. 15 is a top cross-sectional view schematically illustrating anembodiment of a sensor structure including a sensing element which canbe rotated to expose a sensing surface to a process medium.

FIG. 16A is a perspective view of another embodiment of a sensorstructure including a sensing element configured for use in aflow-through arrangement and comprising a storage compartment containinga calibration solution.

FIG. 16B is a side cross-sectional view of the sensor structure of FIG.16A, with the sensor shown in a position in which the sensing element isexposed to calibration solution. FIG. 16C is a side cross-sectional viewof the sensor structure of FIG. 16A, with the sensor shown in a positionin which the sensing element is exposed to an inline flow-cell chamber.

FIGS. 17A and 17B are perspective view of another embodiment of a sensorstructure including a sensing element configured for use in aflow-through arrangement and comprising a storage compartment containinga storage solution. FIG. 17C is a top plan view of the sensor structureof FIG. 17A.

FIG. 17D is a side cross-sectional view of the sensor structure of FIG.17A, taken along the line A-A of FIG. 17C, with the sensor shown in aposition in which the sensing element is exposed to an inline flow-cellchamber.

FIG. 17E is another side cross-sectional view of the sensor structure ofFIG. 17A in the same position as FIG. 17D, taken along the line A-A ofFIG. 17C, with the sensor shown in a position in which the sensingelement is exposed to an inline flow-cell chamber, where the pressurewithin the inline flow-cell chamber causes deformation of a pressureequalization diaphragm.

DETAILED DESCRIPTION

FIG. 1 is a side cross-sectional view schematically illustrating a pHsensing element. The sensing element 100, which may be a pH glasselectrode, includes a body 102 having a half-cell element lead 104 andan internal electrolyte 106 retained within a hollow space within thebody 102, and sealed in place by a seal 108. The sensing element 100 mayalso include or be in electrical communication with a referenceelectrode (not shown).

The distal end of the sensing element 100 includes a pH sensing glasselectrode 110, which serves as a sensing surface of the sensing element100. In some embodiments, this glass electrode 110 can be formed bybeing blown into a bulb shape at the end of the electrode stem glasstubing. By immersing the sensing element into a process medium or othermedium to be measured, such that the sensing surface of the sensingelement is immersed in the process medium, a voltage indicative of thepH of the process medium can be measured.

In some embodiments, a measurement of a process medium retained in abioreactor can be made. In some embodiments, a bioreactor can includerigid walls, and a sensor can be configured such that a sensing elementcan be inserted through a port in the rigid wall of the bioreactor, withthe rigidity of the bioreactor wall providing mechanical support for avariety of different structures or mechanisms used to selectively exposea probe to the process medium therein.

In other embodiments, however, the bioreactor can include a bag or otherflexible structure, which is filled with and retains the process medium.Such a flexible bioreactor may itself be seated within a rigid retainingvessel, but as the walls of the actual containment vessel retaining theprocess medium are flexible, probes and other components which areconfigured to be insertable through or otherwise extend through the wallof the flexible bioreactor.

For example, such components may be configured to be insertable throughreinforced ports in the flexible bioreactor wall, such that thesterility and integrity of the flexible bioreactor are not compromisedduring the insertion process. In some embodiments, sensors may be builtinto the flexible bioreactor bag prior to the bioreactor beingsterilized or filled with a process medium, or otherwise installed priorto the flexible bioreactor being sterilized. Other components, such asagitators, may be similarly insertable through ports in the flexiblebioreactor, or may be provided within the bioreactor prior tosterilization and/or filling of the bioreactor with sterile componentsor media. Because of manner in which a flexible bioreactor such as aflexible single-use bioreactor are manufactured, the sensor or othercomponents of the single-use bioreactor may not be easily accessible tothe end user for the purposes of calibration or performanceverification, as they cannot be removed or retracted without breachingthe sterile barrier.

In some embodiments, a sensor can include a storage compartment orchamber surrounding at least a portion of the sensing element therein,where the sensing surface at the distal end of a sensing element isstored within a storage medium. Storage of the sensing surface of thesensing element, along with other components of the sensor such as areference electrode, may be used to enable deployment of the sensoron-demand, without the need to wet the sensing surface for a period oftime before measurements can be taken. In some embodiments, the storagemedium may also be used as a calibration solution, by using the sensorto take a measurement of the known pH of the storage medium prior todeployment of the sensing element into the process medium. This canallow calibration of the sensor even when the sensor is stored withinthe sealed storage compartment, and inaccessible to the end user. Insome embodiments, a significant period of time may elapse between thetime at which the sensor is sealed into or relative to the sterileenvironment of a single-use bioreactor bag or component to be used withsuch a single-use bioreactor bag, sometimes on the order of severalyears. On-site calibration prior to use of the sensor can be needed toensure that an accurate measurement can be obtained using the sensor.

When a measurement of the process medium is desired, the sensing elementcan be pushed into the process medium, immersing the sensing surface andreference electrode of the sensor into the process medium. In doing so,because the sensing surface of the sensing element is located at thedistal end of the sensing element, the storage solution is exposed tothe process medium, so that any fluid remaining in the storage chamberis intermixed with the process medium. As the storage chamber can besubstantially smaller than the volume of the process medium, the storagemedium will be dispersed into the process medium, and the fluidremaining within the storage chamber, if any, will be substantially thesame composition and pH of the process medium.

In some embodiments, an alternative sensing element design may be used,and the alternative sensing element design may enable a variety ofdifferent single-use sensor designs. FIG. 2 is a side cross-sectionalview schematically illustrating a pH sensing element including a sensingstructure located at a point located away from the end of the structure.The sensing element 200 is similar to the sensing element 100 of FIG. 1,including a body 202 having a hollow space therein, in which a half-cellelement lead 204 and an internal electrolyte 206 are located, and a seal208 retained those components within that hollow space. However, thesensing element 200 differs in that the sensing surface 210, which asdiscussed above may be a glass pH electrode, is located at a point awayfrom the very distal end 218 of the sensing element 200.

In particular, it can be seen that the sensing element 200 includes aproximal portion 212, whose outer surface does not contain a sensingsurface 210, as well as a distal portion 214 which also does not containa sensing surface 210. The sections of the sensing element 200 which donot contain a sensing surface 210, liquid junction, or similarcomponent, may be referred to herein as inactive portions of the sensingelement. The sensing surface 210 may comprise, for example, acylindrical outer section of the body 202 of the sensing element 200,but need not extend around the entire outer perimeter of the body 202.For example, in some embodiments, the sensing surface 210 may be asection of a glass pH electrode or other suitable sensing surface in anydesired shape.

In other embodiments, the sensing surface 210 may comprise glass, metal,electronic components, or any other suitable sensing structure. In someembodiments, the sensing surface 210 may comprise semiconductorcomponents, such as thermistors and resistors, or may compriseintegrated circuits such as ion-sensitive field-effect transistors(ISFETs). The sensing element 200 may be a part of any sensor, includingsensors that reference voltage, current, capacitance, resistance,frequency, or luminescence. Although many embodiments herein aredescribed in the context of pH sensors which can be used with single-useflexible bioreactor bags, embodiments of sensing elements and othercomponents described herein can also be used in a wide range of othersensor types and applications.

The body 202 can be any suitable shape. However, in some embodiments,the body 202 may include a section of substantially constantcross-section extending at least from a point proximal the proximal endof the sensing surface 210, within the proximal section 212 of thesensing element 200, to a point distal the distal end of the sensingsurface 210, within the distal section 214. When viewed incross-section, it can be seen that the outer surface of the sensingsurface 210 is substantially coplanar with the adjacent proximal anddistal sections 212 and 214 of the sensing element 200. As described ingreater detail below, such a sensing element 200 can be translated inthe direction of its longitudinal axis, relative to a storage chamber,while minimizing fluid flow into or out of the storage chamber.

A sensor including the sensing element 200 may also include additionalcomponents not specifically illustrated in FIG. 2. For example, thesensor may include a reference electrode which may in some embodimentsbe integrated within the structure of the sensing element 200 (see, forexample, FIGS. 4A and 4B). In other embodiments, described in moredetail with respect to FIG. 6, a reference electrode may be locatedwithin a separate structure, which may in some embodiments extend alonga parallel longitudinal axis to the longitudinal axis of the sensingelement 200.

FIG. 3A is a side cross-sectional view schematically illustrating asensor structure including a sensing element such as the sensing elementof FIG. 2 and a storage compartment containing a calibration medium. InFIG. 3A, the sensing element 200 is positioned such that it extendsthrough a storage compartment 300 having an internal storage chamber 320filled with a material which serves as both a storage medium and acalibration medium 322. In some embodiments, the storage/calibrationmedium 322 may comprise a fluid, while in other embodiment, other formsof storage/calibration media may be used. For example, if the sensingelement comprises a dissolved oxygen (DO) sensor, thestorage/calibration medium may comprise a gas.

In particular, the sensing element 200 extends through both a proximalaperture of the storage compartment 300 having a proximal sealingelement 310 a positioned therein, and a distal aperture of the storagecompartment 300 having a distal sealing element 310 b positionedtherein. The sensing element 200 extends along a longitudinal axis whichpasses through the centers of the proximal and distal apertures of thestorage compartment 300.

In the position illustrated in FIG. 3A, the sensing element 200 of theprobe is shown in a retracted position, in which the sensing surface 210of the sensing element 200 is disposed within the storage compartment300 and immersed in the storage/calibration medium 322. Because thesensing surface 210 is not located at the distal end 218 of the sensingelement 200, the sensing element 200 includes an inactive distal portion214 which can be exposed to a process medium or any other materialwithout affecting the voltage (or other information) provided by thesensing element 200. In addition, because the inactive distal portion214 does not include a sensing surface 210, the sensing element can bestored with part of the inactive distal portion 214 exposed, withoutaffecting the sensing element 200 or requiring advance preparationbefore the sensing element 200 can be used in a measurement.

In particular, it can be seen in FIG. 3A that the inactive distalportion 214 interacts with the distal sealing element 310 b to form partof the boundary encapsulating the storage/calibration medium 322 withinthe internal storage chamber 320 of the storage compartment 300. This isin contrast to the types of storage configurations required by the useof a sensing element such as the sensing element 100 of FIG. 1, having asensing surface at the distal tip. If the sensing surface were at thedistal end, storage of the sensing element with its distal end exposedwould expose an active section of the sensing element to the exterior ofthe storage chamber, such that it would not be exposed to the storagemedium. This could have a detrimental effect on the operation of thesensing element. In addition, more complex and mechanisms would berequired to allow the sensing surface to be extended into the processmedium to be tested, such as piercing a seal, or otherwise placing theinterior of a storage chamber in fluid communication with the processmedium. Such mechanisms would have irreversible effects on at least thecomposition of the fluid within the storage chamber, either by drainingthe storage chamber or allowing the storage medium to intermix with theprocess medium.

In contrast, the configuration of FIG. 3A allows the sensing element 200to be extended into the process medium, without placing the internalstorage chamber 320 in fluid communication with the exterior of thestorage compartment 300. FIG. 3B is a side cross-sectional viewschematically illustrating the sensor structure of FIG. 3A, with thesensing element displaced to expose the sensing structure. In theposition shown in FIG. 3B, the sensing element 200 has beenlongitudinally translated along the longitudinal axis of the sensingstructure, such that the sensing surface 210 is now located outside ofthe sensing compartment 300. The proximal portion of the sensing element200 now interacts with the distal sealing element 310 b to form part ofthe boundary encapsulating the storage/calibration medium 322 within theinternal storage chamber 320 of the storage compartment 300.

In some embodiments, the proximal and distal sealing elements 310 a and310 b may be O-rings or any other suitable gasket or sealing elementwhich maintains a substantially fluid tight seal even when the sealingelement is being translated therethrough. The tolerance of the O-ringsor other sealing element allows maintenance of the fluid seal eventhough the cross-sectional shape of the sensing element 200 may varysomewhat over the length of the sensing element 200.

During the translation of the sensing element 200 through the distalsealing element 310 b, the seal is maintained, due to the outercross-sectional area of the portion of the sensing element 200 incontact with the distal sealing element 310 b being substantiallyconstant, within the tolerance of the distal sealing element 310 b. Evenif some small amount of fluid is pulled out along with the exposedsection of the sensing element 200, for example due to irregularities inthe shape of the outer surface, the total volume of fluid exchangebetween the interior and the exterior of the storage compartment 300 maybe minimal, and significantly less than embodiments in which the storagecompartment is drained or completely exposed when the sensing element isextended. Thus, the volume of storage/calibration medium 322 pulled outof the storage compartment 300 may be less than substantially the entirevolume of the storage compartment 300, in contrast to single use sensordesigns in which the distal end of the sensing element is an activeportion of the sensing element. In embodiments in which the interior ofthe storage compartment is exposed to the process medium, nearly all ofthe storage medium flows out of the storage compartment 300 due todraining or intermixing with the process medium, the volume of which canbe substantially larger than the volume of the storage medium.

In contrast, through the use of media-retaining storage compartments asdescribed herein, a greater amount of the storage/calibration medium canbe retained after the sensor is extended (and retracted) into thestorage medium. For example, more than 10% of the storage/calibrationmedium may be retained in the storage compartment, more than 30% of thestorage/calibration medium may be retained in the storage compartment,more than 50% of the storage/calibration medium may be retained in thestorage compartment, more than 70% of the storage/calibration medium maybe retained in the storage compartment, more than 90% of thestorage/calibration medium may be retained in the storage compartment,more than 95% of the storage/calibration medium may be retained in thestorage compartment, more than 97% of the storage/calibration medium maybe retained in the storage compartment, more than 98% of thestorage/calibration medium may be retained in the storage compartment,or more than more than 99% of the storage/calibration medium may beretained in the storage compartment.

The sensor structure of FIG. 3A can be integrated into or otherwiseinstalled in a bioreactor such as a flexible single-use bioreactor bag.FIG. 4A is a side cross-sectional view schematically illustrating thesensor structure of FIG. 3A, shown in a sealed position relative tomedia to be tested. It can be seen that the proximal side of the storagecompartment 300 is attached to, integrated with, or otherwise securedrelative to the flexible wall 400 of the bioreactor, such that thestorage compartment 300 is located on the interior of the bioreactor,and extends into the process medium 410. In other embodiments, however,the storage compartment 300 may be located at least partially outside ofthe wall 400 of the bioreactor, or entirely outside the wall of thebioreactor, and a wide variety of suitable configurations may be used.

When the sensing element is in the retracted position of FIG. 4A, thedistal sealing element 310 b maintains a fluid-tight seal between thestorage/calibration medium 322 and the process medium 410. Thecomposition of the storage/calibration medium 322 remains constant andthe pH remains at a known, constant value. At some point prior toextension of the sensing element 420 into the process medium 410, avalidation or calibration process may be performed by measuring thevoltage from the sensing element 200 to confirm that it is consistentwith the expected reading, based on the known pH of thestorage/calibration medium 322.

It can also be seen in FIG. 4A that the sensing element 200 includes anintegrated reference electrode as part of the single structure. Thesensing element 200 includes an internal wall separating a firstinternal region of the body 202 from a second internal region. The firstinternal region includes the half-cell element lead 204 and a volume ofinternal electrolyte 206 in fluid communication with the sensing surface210, while the second internal region includes a half-cell element lead264 and a second volume of internal electrolyte 266 in fluidcommunication with a liquid junction 260. When in the position shown inFIG. 4A, both the sensing surface 210 and the liquid junction 260 are incontact with the storage/calibration medium 322.

The sensing element 200 may be moved in the longitudinal direction tothe position shown in FIG. 4B. During this process, the distal sealingelement 310 b maintains a fluid seal with the constant-diameter sectionof the sensing element 200, preventing or minimizing fluid exchangebetween the storage/calibration medium 322 and the process medium 410.When in the position shown in FIG. 4B, both the sensing surface 210 andthe liquid junction 260 are in contact with the process medium 410, asthe length of travel is sufficient that both the sensing surface 210 andthe liquid junction 260 pass through the sealing element. To maintainthe fluid-tight seal, the section of substantially constantcross-sectional area includes the section of the sensing element 200which includes both the sensing surface 210 and the liquid junction 260.When in the extended position, the pH of the process medium 410 may bemeasured by measuring the voltage from the sensing element 200, when thesensing surface 210 and the liquid junction 260 are immersed in theprocess medium 410.

Once the pH of the process medium 410 is measured, the sensing element200 can then be retracted into the storage compartment 300. The distalsealing element 310 b again operates to prevent or minimize fluidexchange between the storage/calibration medium 322 and the processmedium 410 by maintaining a fluid-tight seal during the retraction. Theshape and configuration of the sensing element 200 allow thestorage/calibration medium 322 to be retained within the storagecompartment 300 even after the extension and retraction of the sensingelement 200. In contrast to other designs in which the storage medium isnot retained, or mixes with the process medium, the sensing surface 210of the sensing element 210 is retained within a storage/calibrationmedium 322 of known composition and pH, due to the lack of significantmixing of the storage/calibration medium 322 with the process medium410. This enables a post-measurement calibration or validation process,in which the voltage from the sensing element 200 is measured to confirmthat it is consistent with an expected reading, based on the known pH ofthe storage/calibration medium 322, to confirm that the probe isoperating correctly. This can be done in a non-destructive fashion,without cutting into the flexible wall 400 or otherwise removing thesensing element 200 from the bioreactor.

By inhibiting fluid flow between the storage/calibration medium 322 andthe process medium 410, a wider range of possible compositions of thestorage/calibration medium 322 may be possible. If a storage compartmentis designed such that all of the storage medium contained therein willbe mixed with the process medium, the composition of the storage mediummay be chosen so that it will have a pH near 7.0 at room temperature, soas to have a minimal effect on the pH or composition of the processmedium. If, however, the storage/calibration medium 322 can be retainedwithin the storage compartment, with minimal if any mixing with theprocess medium, storage/calibration media with a wider range of possiblecompositions and pH may be used. For example, in one embodiment, astorage/calibration medium 322 with a pH of roughly 4.0 at roomtemperature may be used. By providing a larger difference between the pHof the storage/calibration medium 322 and the expected pH of the processmedium 410, an error in the operation of the sensing element will bemore apparent, as the measured voltage will differ from the expectedvoltage by a larger amount.

In other embodiments, storage/calibration media having a pH of 4.01,6.86, 9.18, or 10.05 at room temperature may be used. However, a widevariety of other pH ranges may also be suitable as storage/calibrationmedia. In some embodiments, the pH at room temperature may be between 0and 14, between 1 and 13, between 3 and 12, between 4 and 10.5, between5 and 10.5, or between 6 and 10.5. In some embodiments, the pH at roomtemperature may be less than 6.5, less than 6.0, less than 5.0, or lessthan 4.0.

In embodiments in which the sensing structure comprises a type of sensorother than a pH sensor, the calibration medium may be chosen based onthe property to be measured by the sensor. As discussed above, thecalibration medium may comprise a gas or other material.

Even in the case of a smart sensor, in which the calibration can beperformed prior to sterilization and subsequent installation into aflexible bioreactor bag, and the calibration data stored in a memorycircuit of the smart sensor, the use of the storage medium as acalibration medium can still provide a verification of the continuedfunctionality of the smart sensor, as a measurement sufficientlydifferent from the known pH of the storage medium can provide anindication that the sensor has failed or is otherwise not providing anaccurate measurement of the pH to which the sensing surface is exposed.Because this storage solution is maintained in substantially itsoriginal state, with minimal if any exposure to the process medium, thisverification or failure check can also be performed after the sensingelement is retracted back into the storage chamber. If the pHmeasurement of the process medium is different from an expectedmeasurement, the retraction and subsequent measurement of the sensingelement of the probe when exposed to the storage solution can provide arapid and non-destructive check or verification of the operation of themeasurement probe while the process is still ongoing. Because thecalibration medium is retained in the storage compartment, the sensingelement can be moved to a medium with known pH without the need tocompromise the sterility of the ongoing process by physically removingthe engaged probe structure from the flexible bioreactor andcompromising the sterility of the process medium.

In some embodiments, the shape of the sensing element can be used inconjunction with a dual-chambered storage compartment to providetwo-point on-site calibration of a sensor, or two-point verification.FIG. 5A is a side cross-sectional view schematically illustrating asensor structure including a dual-chamber storage/calibrationcompartment, with the sensing structure of the sensing element locatedin the upper chamber. The storage compartment 500 is similar to thestorage compartment 300 of FIG. 3A, but differs in that it includes aninternal wall separating a distal chamber 520 b from a proximal chamber520 a. The sensing element 200 cooperates with an internal sealingelement 510 c to maintain a seal between the proximal and distalchambers 520 a and 520 b. Because this internal seal will be maintainedduring translation of the sensing element 200 through the storagecompartment 500, with minimal fluid flow between the chambers, theproximal chamber 520 b may retain a storage/calibration medium 522 adifferent from the storage/calibration medium 522 b in the distalchamber 520 b. In some embodiments, one of the chambers may include amedium which functions only as a calibration medium, with the sensingsurface 210 of the sensing element being stored in the other of the twochambers for extended periods of time.

When the pH of the storage/calibration medium 522 a differs from the pHstorage calibration medium 522 b, a two-point validation or calibrationprocess may be performed prior to and/or after measurement of a processmedium. The voltage of the sensing element 200 may be measured when thesensing surface 210 is immersed in the storage/calibration medium 522 a.

The sensing element 210 may then be translated in the distal direction.FIG. 5B is a side cross-sectional view of the sensor structure of FIG.5A, with the sensing structure of the sensing element located in thelower chamber. The voltage of the sensing element 200 may also bemeasured when the sensing surface 210 is immersed in thestorage/calibration medium 522 b. The measured voltage when the sensingsurface 210 is exposed to the storage/calibration media 522 a and 522 bcan be compared with the expected voltages at the known pH values of thestorage/calibration media 522 a and 522 b, and used to verify orcalibrate the sensing element 200.

Once done, the sensing element 200 may then be extended into a processmedium for testing and used for measurement and control of the process.FIG. 5C is a side cross-sectional view of the sensor structure of FIG.5A, with the sensing structure of the sensing element exposed to theexterior of the storage/calibration compartment. After measurement ofthe process medium, the sensing element may then be retracted throughboth chambers 520 a and 520 b, and measurements may be taken in eachchamber as part of a post-measurement validation process.

As discussed elsewhere herein, the sensing structure may also includeadditional components not specifically illustrated in the figures, suchas a reference electrode. FIG. 6 is a side cross-sectional viewschematically illustrating a storage compartment configured to retaintherein a pair of sensing elements oriented parallel to one another. Thestorage compartment 600 differs from the storage compartment 300 of FIG.3A in that the storage compartment 600 includes a pair of proximalsealing elements 610 a and 640 a and a pair of distal sealing elements610 b and 640 b. The sealing elements 610 a and 610 b are dimensionedand spaced to receive the sensing element 200, while the sealingelements 610 b and 610 b are dimensioned and spaced to receive aseparate sensing element 650, which may serve as the reference electrodefor a probe.

The reference half-cell element 650 includes a liquid junction 660, andcan be configured to move along with the sensing element 200 such thatwhen the sensing surface 210 is exposed to the storage/calibrationmedium 322, the liquid junction 660 is as well. Similarly, when thesensing surface 210 is exposed to a process medium 322, the liquidjunction 660 will also be exposed to the process medium. A section ofsubstantially constant cross-sectional area extending to either side ofthe sensing surface 600 allows the sealing element 610 b to maintain afluid-tight seal during translation of the reference half-cell element650 therethrough.

Although the embodiments described herein are primarily described in thecontext of pH sensors in conjunction with bioreactors, the featuresdescribed herein can be utilized in conjunction with other types ofsensors, and in other contexts. For example, in addition to use withbioreactor bags, or tubing or other conduits in fluid communication withbioreactor bags, the sensing elements and associated components may beused with or integrated into a wide variety of other elements in aprocess flow. These elements may be flexible bags or other containersused in media preparation, upstream of a cell culture, as well as invarious purification steps downstream of a cell culture. Similarly,embodiments may be used in any other suitable application, inconjunction with any suitable type of sensor. For example, the storagecompartment and sensing element geometry can be used to facilitateon-site calibration during, for example, field testing of pH or othermeasurements, with the ability to retract the measurement probe into astorage compartment that protects the probe and allows for calibrationor verification of the probe operation before or after tests.

In some embodiments, a storage compartment can include port or otheropening to replace, alter, or otherwise interact with thestorage/calibration medium. FIG. 7 is a side cross-sectional viewschematically illustrating a sensor structure including a sensingelement such as the sensing element of FIG. 2 and a storage compartmentincluding two ports allowing access to the storage medium inside thestorage compartment. The storage compartment 700 includes a first port780 a, which may serve as an inlet port, extending through an aperture770 a in the wall of the storage compartment 700, and a second port 780b, which may serve as an outlet port, extending through an aperture 770b in the wall of the storage compartment 700. The ports 780 a and 780 bmay include filters, which may in some embodiments be submicron filters.The ports 780 a and 780 b allow access to the storage/calibration medium722 within the storage compartment 700 without compromising thesterility of the storage compartment 700. This can be used to replace,refill, or otherwise alter the volume or composition of thestorage/calibration medium 722 within the storage compartment 700.

In certain embodiments discussed herein, the operation of a sensingelement in conjunction with a media-preserving storage and calibrationchamber is discussed in the context of extending the sensing elementinto a flexible bioreactor bag or similar process container to accessthe process medium. In other embodiments, however, the sensing elementmay be used in conjunction with a tube or other component which is influid communication with the process container, or can be selectivelyplaced in fluid communication with the process container. In someembodiments, the sensing element can be extended into a cavity throughwhich process medium or other medium to be tested is flowing.

FIG. 8 is a side cross-sectional view schematically illustrating asensor structure including a sensing element such as the sensing elementof FIG. 2 and a storage compartment, where the storage compartment isdisposed adjacent a portion of a fluid path. In FIG. 8, the storagecompartment 300 is located adjacent a fluid or gas conduit 800, suchthat the sensing element 200 can extend into the conduit 800 and exposethe sensing surface 210 (and liquid junction 260, if integrated withinthe sensing element 200) into the medium 822 within the conduit 800. Insome embodiments, the medium 822 may be flowing through the conduit 800during at least part of this process.

In the illustrated embodiment, the conduit 800 includes a section 820having a larger cross-sectional area than adjacent sections 880 of theconduit 800. Such a configuration can be used when the cross-sectionalarea of the conduit 800 is small enough relative to the size of theexposed portion of the sensing element 200 that the sensing element 200could not extend a sufficient distance into the conduit 800 to exposethe sensing surface 210 and liquid junction 260, or would significantlyocclude the flow of the medium 822 through the conduit 800. Inembodiments in which the medium 822 is flowing through the conduit 800,the sensing element 200 may remain in an extended position to measure aproperty of the medium 822 at multiple points in time. Multiplemeasurements over a period of time may also be made in any of theembodiments discussed herein, such as to measure the progress of aprocess over time.

In other embodiments, the sensing element need not be cylindrical, butmay be any suitable shape. FIG. 9A is a perspective view schematicallyillustrating another embodiment of a sensing element. FIG. 9B is a sideview schematically illustrating the sensing element of FIG. 9A. Thesensing element 900 includes a planar side 902, and a sensing surface910 located on or in the planar side 902. In the illustrated embodiment,the sensing element 900 is in the shape of a rectangular prism, but inother embodiments, any other suitable shape may be used. The side havingthe sensing surface 910 need not be planar, but may be any suitableshape, as described in greater detail below. The sensing element 900 mayalso include a half-cell element lead and an internal electrolyte, asdiscussed elsewhere herein, and may also include an integrated referenceelectrode, which may include a liquid junction adjacent the sensingsurface 910.

FIG. 10A is a side cross-sectional view schematically illustrating asensor structure including the sensing element of FIG. 9A, shown in aposition in which the sensing structure is exposed to astorage/calibration medium. FIG. 10B is a cross-sectional view of thesensor structure of FIG. 10A, taken along the line 10B-10B of FIG. 10A.The sensor structure 1000 includes a pair of apertures 1012 a and 1012b, surrounded by sealing elements 1010 a and 1010 b, respectively. Thesealing elements may comprise O-rings or other gaskets, or any othersuitable sealing structure. One aperture is in fluid communication witha storage compartment 1020 containing a storage medium 1022, which mayalso serve as a calibration medium. The other aperture is in fluidcommunication with an area which may be filled with or otherwise exposedto a process medium to be tested. The planar side 902 of the sensingelement cooperates with the sealing element 1010 a to retain thestorage/calibration medium 1022 within the storage compartment 1020. Inthe position shown in FIG. 10A, the sensing surface 910 of the sensingelement 900 is exposed to the storage/calibration medium in the storagecompartment 1020.

FIG. 10C is a side view of the sensor structure of FIG. 10A, with thesensing element moved to a position in which the sensing surface can beexposed to a process medium. The sensing element 900 is translated in adirection parallel to the planar side 902, such that the planar side 902slides along the sealing elements 1010 a and 1010 b until the sensingsurface 910 is aligned with the aperture 1012 b, allowing exposure ofthe sensing surface 910 to a process medium to be tested.

FIG. 11A is a side view of another embodiment of a sensor structureincluding a sensing element such as the sensing element of FIG. 2 and astorage compartment containing a storage solution, shown inserted into atube port. FIG. 11B is a perspective view of the sensor structure ofFIG. 11A.

The sensor structure 1500 may be a single-use sensor such as asingle-use pH sensor, and includes a sensor housing 1502 which includesa storage compartment 1540 containing a storage solution 1542. Thesensor housing 1502 can be secured relative to a tube port 1400 asshown, or other suitable structure. The sensor structure 1500 alsoincludes a movable component 1504 which is longitudinally translatablerelative to the sensor housing 1502, and which supports a sensingelement 1520 such as the sensing element 200 of FIG. 2.

A sealing element such as an external gasket 1528 or O-ring cooperateswith the internal surface of the tube port 1400 to maintain theintegrity of the bioreactor bag in which the tube port 1400 isinstalled. To illustrate the fit of sensor structure 1500 within tubeport 1400, FIG. 11A shows the tube port 1400 in partial cutaway view,whereas FIG. 11B shows the external surface of the tube port 1500. Theexternal gasket 1528 is located between the sensor housing 1502 and thetube port 1400, and does not extend through the interior of the storagecompartment 1540 or contact the storage solution 1542 inside. Aconnector 1580 extending from the proximal end of the sensor structure1500 allows connections to be made with an external instrument orsystem.

Translation of the movable component 1504 of the sensor structure 1500allows the sensing element 1520 to be translated moved from a firstposition in which the sensing surface 1522 of the sensing element 1520is retained within the storage compartment 1540 and exposed to thestorage solution 1542. The sensing element 1520 can be moved to a secondposition in which the sensing surface 1522 has been translated throughthe distal internal gasket near the distal tip 1510 of the sensorhousing 1502, allowing exposure of the sensing surface 1522 to a processmedium.

Control over the longitudinal translation of the movable component 1504and the sensing element 1520 with respect to the sensor housing 1502 canbe provided through the use of an outwardly extending bolt 1552 or otherfeature which is retained within a longitudinally-extending aperture1590 in the sensor housing 1502. In the illustrated embodiment, theaperture 1590 includes a distal wider region 1592 a and a proximal widerregion 1592 b connected to one another by a narrower longitudinalchannel 1594. The aperture 1590 can be dimensioned, in conjunction withother components and features of the sensor structure 1500, to define orconstrain the manner in which the movable component 1504 can be movedrelative to the sensor housing 1502.

In one embodiment, the bolt 1552 may have a shape which varies over theheight of the bolt, and may be resiliently supported by a cantileveredportion of the movable component. In particular, an upper section of thebolt 1552 may have a narrower section, allowing it to be translatablealong the narrower longitudinal channel 1594 when the bolt 1552 ispressed inwards. When the bolt is no longer pressed inwards, it willflex back outwards, and the thicker lower section of the bolt 1552 willretain the bolt in place within one of the wider regions 1592 a or 1592b. Outwardly extending grips or wings 1554 can assist with translationof the movable component of the sensor 1500 relative to the housing, andmay be movable through longitudinal channels in the sensor housing 1502.

Other configurations are possible, as well. In another embodiment, thebolt 1552 or similar structure may include a rotatable section, suchthat the bolt must be rotated to a particular position to betranslatable along the narrower longitudinal channel 1594, and can thenbe rotated back once in place in one of the wider regions 1592 a or 1592b to retain the movable component of the sensor 1500 relative to thesensor housing 1502.

FIG. 11C is a perspective view of an embodiment in which a supplementalsecurement device is used to secure the single-use sensor relative tothe tube port. It can be seen in FIG. 11C that a length of tubing 1450extends over the point at which the proximal end of the tube port abutsa facing surface of the sensor housing 1502. A first compressive member1442 is located proximal the flared proximal portion 1530 of the sensorhousing 1502 and a second compressive member 1444 is located distal theflared portion 1430 of the tube port 1400 which abuts the flared portion1530 of the sensor housing 1502. In some embodiments, the compressivemembers 1442 and 1444 comprise zip ties, bands, or similar structures.

The compressive members 1442 and 1444 crimp the outer edges of thetubing 1450 and cooperate with the flared sections of the collarportions 1430 and 1530 to prevent the single use sensor 1500 from beingremoved from the tube port 1400. Other suitable retention methods canalso be used, including snap fit or clamshell type devices which can fitover the abutting portions of the sensor 1500 and the tube port 1400. Atleast a portion of the tubing 1450 may be translucent or transparent tofacilitate detection of leaks between the tube port 1400 and the sensor1500.

FIGS. 12A and 12B are cutaway figures which illustrate the internalcomponents of the sensor structure of FIGS. 11A to 11C in both aretracted and extended configuration. In FIG. 12A, it can be seen thatthe distal tip 1510 of the sensor housing 1502 has a smallercross-sectional area than the remainder of the sensor housing 1502, andthat the distal internal gasket 1512 is secured within the region ofsmaller cross sectional size. By reducing the cross-sectional size ofthe sensor housing 1502 at the distal tip 1510, the smaller distalinternal gasket 1512 can be used to maintain a seal without the need toform a thicker section of the sensor housing wall. In other embodiments,however, the thickness of the wall of the sensor housing near the distaltip 1510 may be increase to provide a similarly-shaped interior space,with a wider outer cross-sectional shape. In addition, the size of theseal formed between the distal internal gasket 1512 and the sidewall ofthe sensing element 1520 is reduced, decreasing the possibility or theamount of leakage of storage solution 1542 from the storage chamber1540.

It can also be seen that when the movable component 1504 is in theretracted position, the tip of the sensing element 1520 is pulled backwithin the space between the distal internal gasket 1512 and the edge ofthe distal tip 1510 of the sensor housing 1502, which may provideadditional protection against damage to the sensor element and possibledisruption of the seal between the distal internal gasket and the sensorelement. In some embodiments, a protective structure such as a bumper orguard pins could overlie at least a portion of the tip of the sensingelement. The use of a blunt protective structure can avoid perforationof a bioreactor bag in a folded position.

The proximal end of the storage compartment 1540 is defined by a plug1560 including a proximal internal gasket 1562 which cooperates with theinternal sidewall of the sensor housing 1502 to retain the storagesolution 1542 within the storage compartment 1540. A passage extendingthrough the plug 1560, which may include an internal gasket (not shown)allows a plunger 1564 supporting and retaining the sensing element 1520to be translated longitudinally through the plug 1560 as the movablecomponent 1504 is moved.

As can be seen in FIG. 12B, when the sensing element 1520 is in anextended position, a portion of the plunger 1564 which was originallylocated proximal of the plug 1560 is now extending into and in contactwith the interior of the storage compartment 1540 and exposed to thestorage solution 1542. In order to maintain the sterility of the storagechamber 1540, a bellows structure 1570 located proximal of the plug 1560define a sterile and compressible area within which a proximal portionof the plunger 1564 is retained when the sensing element 1520 is in anunextended or retracted position.

In some embodiments, the sensing element may be a part of a smart sensoror similar structure, which includes, among other components, a memorycircuit. In some embodiments, this memory can also be used to validatethe operational history of such a smart sensor. Inadvertent or mistimedmovement of the movable element of such a smart sensor that results inretraction of the sensing surface from the process media during theprocess can compromise the integrity of the sensor measurement and canaffect the operation or outcome of a bioprocess with which the sensor isused.

In some embodiments, where feedback from a pH or similar sensor is usedto manage a bioprocess, early or delayed exposure of the sensing surfaceto the process medium can cause the bioprocess to be incorrectlycontrolled. If a problem occurs with a bioreactor run, it may benecessary to demonstrate the root cause of this issue. By monitoring orrecording indications that the sensing element was extended, theoperational history of such a sensor can be monitored and preserved.

In some embodiments, the sensor can include a mechanism for detectingmovement of the sensing element or another movable component of thesensor relative to the sensor housing. In one embodiment, this movementdetection mechanism may include a mechanical contact, a proximityswitch, or any other suitable mechanism for detecting or providing anindication of the relative position of a component of the sensor.

In some particular embodiments, movement of the movable component awayfrom a particular position may be detected, while in other embodiments,movement to a particular position or past a particular position may bedetected. In some embodiments, multiple detection mechanisms may beincluded, such as a first detection mechanism configured to detectmovement of a component to or away from a first position, and a seconddetection mechanism configured to detect movement of the component to oraway from a second position.

In an embodiment of a sensor structure such as the sensor structure ofFIGS. 11A-12B, movement of the sensing element 1520 can be detected viaone or more movement detection mechanisms. These movement detectionmechanisms need not be located on or adjacent the sensing elementitself, but may instead be located, in some embodiments, proximal of theentire sensing element 1520. For example, the detection sensors may besupported by or adjacent another portion of the movable component 1504,as the attachment of the sensing element 1520 to movable component 1504means that there is a direct correlation between translation of themovable component 1504 and translation of the sensing element 1520supported by the movable component 1504. Thus the movement and positionof the sensing element 1520 can be indirectly but precisely monitored bymonitoring the movement or position of another portion of movablecomponent 1504.

Upon detection of movement indicative that the sensing element has beenmoved relative to the sensor housing, time-stamped information relatingto the movement of the sensing element may be written to or otherwiserecorded in the memory of the smart sensor. In an embodiment in whichthe smart sensor is connected to or otherwise in communication with anexternal instrument, such information may be transmitted to the externalinstrument or system, where it can be stored in the memory of theexternal instrument or device. In some embodiments, even a sensorwithout an included memory can include movement detection mechanismsavailable to be used by an external instrument to detect and recordmovement of the sensing element when the sensor is connected to theexternal instrument. In this way, a log or other record can begenerated, indicative of the movement of the sensing element and thetimes at which that movement occurred.

In embodiments in which the sensor structure is gamma ray sterilized,the exposure to gamma radiation may place constraints on the type ofcircuitry which can be included in the sensor structure itself. In oneembodiment, the sensor structure may include a robust memory chipcapable of withstanding gamma radiation, as well as a movement detectionmechanism which can be utilized in conjunction with a connected externalinstrument or other connected instrumentation, such as galvanic contactswhich are closed when the sensor is in a particular position. Theconnected instrument can detect movement of a component of the sensorstructure to or away from a given position, and record timestampedinformation regarding this movement to the memory chip within the sensorstructure. In such an embodiment, an event log can be maintained withinthe robust memory chip included in the sensor structure.

In some embodiments, the connected instrumentation may include a dongleor other component which can be attached to the connector after thebioreactor bag is set up, and which includes circuitry which isconfigured to operate in connection with a hardened memory chip and oneor more movement detection mechanisms to record to the hardened memorychip information relating to detected movement. By including thiscircuitry in a supplemental component, the circuitry in the supplementalcomponent need not be made sufficiently robust to withstand the gammaray sterilization process. The supplemental component can in someembodiments remain in place when a connection is made to other externalinstrumentation, such as by connecting the external instrumentation andthe supplemental component in series.

In some embodiments, the detection of motion by an external instrumentneed not be contemporaneous with the occurrence of the motion. Forexample, in some embodiments, the movement detection mechanism mayinclude a circuit and/or a mechanical component which can be tripped orotherwise altered by movement of a component of the sensor relative tothe sensor housing. Such a circuit and/or component may be altered in amanner which can be detected by an external instrument, or directlyobserved by a user. This alteration may in some embodiments provide anindication of the time at which the movement occurred.

In some devices, a mechanical interlock or similar feature can be usedto prevent retraction of a sensing element without operator assistance,to prevent inadvertent termination of process media sensing. Detectingand recording information relating to the timing movement of the sensingelement can provide additional protection beyond or in addition toprotection provided by a mechanical interlock. The movement record thusgenerated can be helpful in documenting both abnormal and successfulbioreactor runs. This tracking can also provide an additional check asto the proper handling and sterility of a single-use sensor before use.

In some embodiments, the sensor output may also be used to provide anindication of movement of the sensing surface in or out of the storagecompartment. If the sensor output is continually or periodicallymonitored, the smart sensor can detect a deviation from the sensoroutput corresponding to immersion in the storage medium, and can record,for example, a timestamp or similar information indicative of theinsertion time of the sensor. This sensor exposure timestamp or similarinformation can provide another record of the process timeline.

In some embodiments, the storage solution is a reference solution, suchas the reference solution used in the sensing element itself. In otherembodiments, the storage solution may be a pH buffered storage solution.Because the storage medium is a sealed compartment, the pH and othercharacteristics of the storage medium will remain constant while thesensing element is retained within the storage and calibration chamber.At the point of time at which the sensing element is pushed into theprocess medium, the sensing surface and reference electrode of thesensor are immersed in the process medium, which will havecharacteristics different than the characteristics of the storagemedium. Upon exposure to the process medium, the sensor output willdeviate from the substantially constant sensor output which resultedfrom immersion in the storage medium.

This deviation from the constant sensor output while immersed in thestorage medium provides an indication that the sensor has been insertedinto the process medium, or that the storage medium has becomecompromised, and can be used to provide additional validation of boththe integrity of the storage compartment and of the time at which thesensor was first extended into the process medium. Because the storagemedium will in many embodiments have characteristics which aresubstantially different from the process medium, retraction of thesensing element into the storage medium can also be detected by a returnof the sensor output to a sensor output similar to the substantiallyconstant sensor output which resulted from immersion in the storagemedium.

FIG. 13A is a side view of another embodiment of a sensor structureincluding a sensing element such as the sensing element of FIG. 2 and astorage compartment containing a storage solution, configured to beinserted into a tube port. FIG. 13B is a side view of the sensor of FIG.13A, shown in an extended position. FIG. 14A is a cross-sectionalperspective view of the sensor structure of FIG. 13A, shown in aretracted position. FIG. 14B is a cross-sectional perspective view ofthe sensor structure of FIG. 13A, shown in an extended position.

The sensor structure 1700 is similar to sensor structure 1500 in certainaspects, and like sensor structure 1500, the sensor structure 1700 maybe a single-use sensor such as a single-use pH sensor, including asensor housing 1702 which includes a storage compartment 1740 containinga storage solution. The sensor housing 1502 can be secured relative to atube port 1400 as shown, or other suitable structure. The sensorstructure 1700 includes a movable component which is longitudinallytranslatable relative to the sensor housing 1702.

The movable component supports a sensing element 1720 having a sensingsurface 1722 such as the sensing element 200 of FIG. 2. One or moreexternal gaskets or O-rings can be used to cooperate with the internalsurface of a tube port to maintain the integrity of the bioreactor bagin which the tube port is installed, as described below.

A connector 1780 extends from the proximal end of the sensor structure1700. The connector 1780 differs from the connector 1580 of the sensorstructure 1500 in that the connector 1780 includes a length of cabling1782 extending between the proximal end of the sensing element 1720 andthe connector interface 1784 at the proximal end of the connector 1780.In some embodiments, a sensor structure 1700 may be provided with onlythe connected cabling 1782, and a desired connector interface for usewith a particular external instrument or system may be attached at alater point in time.

The interface mechanism for translating the movable component of thesensor structure 1700 also differs from that of the sensor structure1500. As can be seen, the interface mechanism of sensor structure 1700includes a throw lever 1790, comprising a generally U-shaped handleoperably coupled at the end of both arms to the upper housing section1792, which in the illustrated embodiment serves as the movablecomponent of the sensor structure 1792 and supports the sensing element1720 near the proximal end of the sensing element 1720. The throw lever1790 may facilitate operation of the sensor structure 1700 while a useris wearing gloves, or when there are other impediments to interactionwith the sensor structure.

The throw lever 1790 is movable between a first position, shown in FIG.12A, in which the throw lever 1790 lies against or adjacent a proximalsection of the upper housing section 1792, and a second position, shownin FIG. 12B, in which the throw lever 1790 lies against or adjacent adistal section of the upper housing section 1792. The throw lever 1790is operably coupled via a suitable mechanical linkage, cam surfaces, oranother suitable mechanical arrangement to the movable component of thesensor structure 1700. Raised features 1794 on the surface of the upperhousing section 1792 may cooperate with the throw lever 1790 to providesome resistance against inadvertent movement away from a desiredposition of the throw lever 1790.

The shape of the upper housing section 1792, and in particular thegenerally cylindrical sidewall section of the upper housing section 1792underlying the throw lever 1790, cooperates with the shape of the throwlever 1790 to constrain the positions to which the throw lever 1790 canbe moved. Because the throw lever 1790 is operably coupled to themovable component of the sensor structure 1700, constraint on the travelrange of the throw lever 1790 constrains the longitudinal translation ofthe movable component, which in turn constrains the longitudinaltranslation of the supported sensing element 1720.

The shape of the distal section of the sensor housing 1702 also differsfrom the shape of the distal section of the sensor housing 1502 of thesensor structure 1500. In contrast to the sensor housing 1502, whichincludes a single flared section 1530 of the sensor housing 1502, thesensor housing 1702 includes a proximal flared section 1730 having adistal surface 1732 which can abut a proximal surface of a tube port,but also includes a ridged section 1734 formed from a resilient materialsuch as silicone rubber and having ridges of increasingly largerdiameter in the proximal direction. The flexible ridged section can abuta internal surface of a tube port to ensure a fluid seal will be formeddespite variations in the internal cross-sectional size of the tubeport, or imperfections in the interior surface of the tube port.

In other embodiments, movement of the sensing element to selectivelyexpose the sensing surface to the process medium and to thestorage/calibration medium may include rotation of the sensing element,in addition to or in place of translation of the sensing element in agiven direction. FIG. 15 is a top cross-sectional view schematicallyillustrating a sensor structure including a sensing element which can berotated to expose an active portion of the sensing surface to a processmedium. The sensor structure includes a cylindrical sensing element 1200including a sensing surface 1210 which does not extend around the entirecircumference of the sensing element 1200. The sensing element 1200 canalso include a half-cell element lead and an internal electrolyte, asdiscussed elsewhere herein, and may also include an integrated referenceelectrode. In some embodiments, the sensing surface 1210 extends aroundless than half the circumference of the sensing surface 1200, althoughin other embodiments it can extend around substantially less than halfthe circumference of the sensing element 1200, as shown in FIG. 15.

The surface of the sensing element 1200 is in contact with a firstsealing element 1212 a and a second sealing element 1212 b. The firstsealing element 1212 a cooperates with the surface of the sensingelement 1200 to seal a storage compartment 1220 containing astorage/calibration medium 1222. The second sealing element extendsaround an aperture in fluid communication with a space 1290 which can befilled with or otherwise exposed to a process medium. By rotating thesensing element 1200 relative to the sealing elements 1212 a and 1212 b,the sensing surface 1210 of the sensing element 1200 can be movedbetween a first position in which it is in fluid communication with thestorage/calibration medium 1222 of the storage compartment 1120, and asecond position in which the sensing surface 1210 is circumscribed bythe second sealing element 1212 b to allow the sensing surface 1210 tobe exposed to the process medium in the space 1290.

Regardless of the direction of rotation or translation of the sensingelement, a fluid-tight seal can be maintained during movement of thesensing element as long as the portion of the sensing element in contactwith a sealing element has a substantially constant shape. The portionsof the sensing element which will not contact the sealing element neednot have a substantially constant shape. Thus, portions of the sensingelement 200 of FIG. 2 which are located sufficiently proximal or distalthe sensing surface (or other portions which will contact a sealingelement) can have a varying cross-sectional shape. Similarly, only aportion of the sensing element 1200 of FIG. 15 may have an outer surfacein the shape of a circular arc, while the other surfaces may be anysuitable shape, so long as the sealing elements do not contact thoseportions of the sensing element during movement of the sensing element.Similarly, a sealing element may be configured to maintain asubstantially fluid-tight seal when in contact with a portion of asensing element with a surface having a particular surface profile orshape. As long as the profile of the portion of the sensing elementcontacting the fluid-tight seal has a substantially constant surfaceprofile or shape, the substantially fluid-tight seal can be maintainedduring translation and/or rotation of the sensing element, due to thesealing element cooperating with the surface of the sealing element.

Mechanical stops or other movement-constraining structures or devicesmay be included to prevent the sensing element from being translated toa position where the shape of the section of the sensing element incontact with the sealing element changes. In addition, some variance inshape may be tolerated due to the tolerance of the sealing element.

FIG. 16A is a perspective view of another embodiment of a sensorstructure including a sensing element configured for use in aflow-through arrangement and comprising a storage compartment containinga storage solution. FIG. 16B is a side cross-sectional view of thesensor structure of FIG. 16A, with the sensor shown in a position inwhich the sensing element is exposed to storage solution. FIG. 16C is aside cross-sectional view of the sensor structure of FIG. 16A, with thesensor shown in a position in which the sensing element is exposed to aninline flow-cell chamber.

The sensor structure 2200 comprises a rotatable sensor drum 2220 securedwithin a sensor housing 2202. The sensor housing 2202 comprises an inlet2212 and an outlet 2214. The inlet 2212 and the outlet 2214 are in fluidcommunication with one another via the inline flow-cell chamber 2210,which includes an upper aperture adjacent the facing lower surface ofthe rotatable sensor drum 2220. Although referred to as an inlet 2212and an outlet 2214, the flow direction into and out of the inlineflow-cell chamber 2210 may in some embodiments go in either direction

The sensor structure 2200 includes a connector 2280 extending upwardsfrom the rotatable sensor drum 2200. This connector 2280 can be used toplace the sensor structure in communication with an external instrumentor other system. In the illustrated embodiment, the connector 2290 isoffset from an axis of rotation of the rotatable sensor drum 2220 but inother embodiment, the connector 2280 may be aligned with the axis ofrotation of the rotatable sensor drum 2220.

The rotatable sensor drum 2220 in the illustrated embodiment includes awider lower portion 2222 of larger cross-sectional area than a narrowerupper neck portion 2224. A collar 2204 secured to the sensor housing2202 and having a central aperture that is substantially equal incross-sectional size to the cross-sectional size of the upper neckregion 2224 and smaller than the cross-sectional size of the lowerportion 2222 of the sensor drum 2220 retains the rotatable sensor drum2220 in place. Because the central aperture of the collar 2204 isaligned with the axis of rotation of the sensor drum 2220, and becausethe portions of the sensor drum retained within the sensor housing 2204are rotationally symmetric, the sensor drum 2220 can be rotated withinthe sensor housing 2202. In the illustrated embodiment, a collar gasket2208 provides a seal below the threaded connections between the collar2204 and the sensor housing 2202.

In the illustrated embodiment, an outwardly extending lever 2270 isattached to the sensor drum 2220 to facilitate rotation of the sensordrum 2220. In other embodiments, the sensor drum may be rotated withoutthe lever 2270, or another suitable mechanism may be provided tofacilitate rotation of the sensor drum, such as mechanical featureswhich may be gripped by a user, or which may engage another mechanismused to rotate the sensor drum 2220.

The lever 2270 cooperates with other features of the sensor housing 2202to constrain rotation of the sensor drum. In the illustratedimplementation, the sensor housing 2202 comprises a raised wall 2280extending around a portion of the sensor housing 2202 and extending intothe swept area of the lever 2270. In the illustrated embodiment, thelateral edges of the wall 2280 are complementary with the shape of thelever 2270 such that the wall 2280 defines a first rotational positionof the sensor drum 2220 when the lever 2270 is in contact with a firstlateral edge 2282 of the wall 2280 and a second rotational position ofthe sensor drum 2220 when the lever 2270 is in contact with a secondlateral edge 2284 of the wall 2280.

One or more pins 2286 can be used to constrain movement of the lever2270, such as retaining the lever 2270 in one of the first or secondpositions adjacent a lateral edge of the wall 2280. The pins 2286 may beremovable or may be spring loaded or otherwise biased into the sweptarea of the lever 2270, and movable out of the swept area to allow thelever 2270 to pass thereby when desired.

FIG. 16B is a cross-sectional view illustrating the sensor structure2200 in a first configuration, where the sensor drum 2220 is in a firstposition. In the first position, the flat sensing surface 2230 generallyflush with the base 2228 of the rotatable sensor drum 2220 and exposedat the base 2228 of the rotatable sensor drum 2220 is aligned with astorage and/or calibration chamber 2240 including a storage medium 2240to which the flat sensing surface 2230 is exposed when the sensorstructure is in the first configuration. The flat sensing surface 2230serves as the sensing surface of the sensor structure 2200, allowingcalibration of the sensor structure 2200 when the sensor structure 2200is in this first calibration.

The sensor drum 2220 also contains the remainder of the sensing elementof the sensor structure 2200. Unlike the sensing element of FIG. 2, forexample, the flat sensing surface 2320 of the sensor 2232, a combinationpH electrode. An internal chamber within the sensor drum 2220 contains areference solution 2234 to which the reference electrode of the sensor2232 of the sensing element is exposed. An electrode gasket 2236surrounding the flat sensing surface 2230 prevents leakage of thereference solution 2234 through the base 2228 of the sensor drum 2220and an internal gasket 2238 prevents leakage of the reference solution2234 between other components of the sensor drum 2220 joined together todefine the internal chamber of the sensor drum 2220.

The portion of the base 2228 overlying the inline flow-cell chamber 2210cooperates with the portion of the sensor housing 2204 surrounding theinline flow-cell chamber 2210 and with the outlet gasket 2218 to allowprocess media flowing through the inline flow-cell chamber 2210 to passthrough the inline flow-cell chamber 2210 without interference orleakage.

In FIG. 16C, the sensor drum has been rotated to expose the flat sensingsurface 2230 to the inline flow-cell chamber 2210, placing the sensingsurface of the sensing element of the sensor structure 2200 in fluidcommunication with the inline flow-cell chamber 2210, in a secondconfiguration of the sensor structure 2220. The base 2228 of the sensordrum 2220 seals the storage medium 2242 within the storage compartment2240 when the sensor component 2200 is in this second configuration.

As discussed above, rotation of the sensor drum from the first positionto the second position may include moving the lever 2270 from a firstposition in which it abuts a first lateral end of the wall 2280 to asecond position in which it abuts the second lateral end of the wall2280. The wall 2280 may thus define the complete travel range of thesensor drum 2220, with the first and second positions of the sensor drumcorresponding to the edges of this maximum travel range.

The relative positioning between the storage chamber 2240 and the inlineflow-cell chamber 2210 may correspond to the arc defined by the wall2280. The storage chamber 2240 and the inline flow-cell chamber 2210 arelocated substantially the same distance laterally outward of the axis ofrotation of the sensor drum 2220, so that the flat sensing surface 2230can be selectively exposed, through rotation of the sensor drum 2220, toboth the storage chamber 2240 and the inline flow-cell chamber 2210.

In the illustrated embodiment, the travel range of the sensor drum isroughly 180 degrees, and the storage chamber 2240 and the inlineflow-cell chamber 2210 are located on opposite sides of the axis ofrotation of the sensor drum 2220. In an embodiment in which the storagechamber 2240 and the inline flow-cell chamber 2210 are located at someother angle to one another, the shape of wall 2280 may be adjusted sothat it defines a matching arc. In some embodiments, the entire wall2280 need not be included, as long as features defining stops for therotation of the sensor drum are included.

Note that, although the figures depict the sensor structure 2200 in anorientation in which the axis of rotation of the sensor drum 2220 isvertical, the sensor structure 2220 can in use be oriented in a positionsuch as a position in which the axis of rotation of the sensor drum 2220is horizontal or canted at another angle to the vertical. In such ahorizontal configuration, for example, contact between the storagemedium 2242 within the storage compartment 2240 and the flat sensingsurface 2230 can be ensured.

In an embodiment in which a movement detection mechanism is included inthe sensor structure, the movement detection mechanism may be supportedby or attached to at least one of the lever or wall. Like the 1:1translation of a longitudinally translatable component supporting thesensor element, the angular rotation of the lever will correspond toidentical angular rotation of the sensor drum and the included sensingsurface, and detection of rotational movement anywhere on the sensordrum or attached structures will correspond to rotational movement ofthe sensor drum.

FIGS. 17A and 17B are perspective view of another embodiment of a sensorstructure including a sensing element configured for use in aflow-through arrangement and comprising a storage compartment containinga storage solution. FIG. 17C is a top plan view of the sensor structureof FIG. 17A. 17D is a side cross-sectional view of the sensor structureof FIG. 17A, with the sensor shown in a position in which the sensingelement is exposed to an inline flow-cell chamber. FIG. 17E is anotherside cross-sectional view of the sensor structure of FIG. 17A in thesame position as FIG. 17D, with the sensor shown in a position in whichthe sensing element is exposed to an inline flow-cell chamber, where thepressure within the inline flow-cell chamber causes deformation of apressure equalization diaphragm.

In some embodiments, an inline flow sensor can be exposed to significantpressure within the inline flow-cell chamber. If the pressure within theflow-cell chamber is significantly higher than the surrounding pressure,or the pressure of surrounding chambers, this pressure differential cancompromise both the sterility and the sanitation of the flow-throughsensor structure. The sensor structure may include structures such as aceramic wicks which electrically connect the reference solution to theprocess solution within the inline flow-cell chamber. When the inlineflow-cell chamber is at a pressure significantly higher than thereference solution chamber, this pressure differential can affect theoperation of the sensor structure. In particular, such a pressuredifferential can cause the process solution to backflow through theceramic wicks into the reference solution. This can cause drift of pHmeasurements due to a change in properties of the reference solution,and can affect the sterility and sanitation of the flow through sensor.

FIGS. 17A and 17B are perspectives view of another embodiment of asensor structure including a sensing element configured for use in aflow-through arrangement and comprising a storage compartment containinga storage solution, with a pressure equalization mechanism in fluidcommunication with the inline flow-cell chamber. The sensor structure2300, like the sensor structure 2200 of FIG. 16A, comprises a rotatablesensor drum 2320 secured within a sensor housing 2302, with the sensorhousing 2302 comprising an inlet 2312 and an outlet 2314. The inlet 2312and the outlet 2314 are in fluid communication with one another via theinline flow-cell chamber 2310, which includes an upper aperture adjacentthe facing lower surface of the rotatable sensor drum 2220. Althoughreferred to as an inlet 2312 and an outlet 2314, the flow direction intoand out of the inline flow-cell chamber 2310 may in some embodiments goin either direction

The sensor structure 2300 includes a connector 2390 extending upwardsfrom the rotatable sensor drum 2320. This connector 2390 can be used toplace the sensor structure in communication with an external instrumentor other system. In the illustrated embodiment, the connector 2390includes a flexible cord 2392 with a plug 2394 at its distal tip. Asdiscussed above, the connector 2390 may include a robust memory chipcapable of withstanding gamma radiation, which can be utilized inconjunction with a connected external instrument or other connectedinstrumentation, to provide smart probe functionality to the sensorstructure 2300. As can be seen in FIG. 17D, the robust memory chip 2396can be disposed within the plug 2394 at the end of the connector 2390,although in other embodiments such a memory chip can be locatedelsewhere within or adjacent the sensor structure 2300.

For example, the gamma-hardened chip may include calibration informationsuch as the pH of the storage solution, or other information regardingthe sensor structure 2300, such as the date of manufacture. Because sucha robust memory chip may be able to withstand gamma irradiation, theentire sensor structure can be gamma irradiated while still providingsmart probe functionality out of the box. In addition, a connectedinstrument can record timestamped information regarding the use of thesensor structure, to provide an event log within the robust memory chipfor the purposes of validation.

In the illustrated embodiment, an outwardly extending lever 2370extending upwardly from the sensor drum 2320 can be used to facilitaterotation of the sensor drum 2320. In the illustrated embodiment, thelever 2370 can be moved from a first position in which the sensingsurface 2330 of the sensor 2332 is placed in fluid communication withthe inline flow-cell chamber 2310, as show in FIGS. 17A-17E, to a secondposition in which the sensing surface 2330 of the sensor 2332 is placedin fluid communication with the storage and/or calibration chamber 2240including a storage medium 2242. In the illustrated embodiment, thelever 2370 can be used to rotate the sensor drum 2320 be moved roughly90° to move between the first and second positions. Markings on theexterior of the sensor structure 2300 can be used to indicate thecurrent configuration of the sensor structure 2300 and the manner inwhich it can be changed to a different configuration.

In FIG. 17D, it can be seen that a pressure equalization mechanism islocated within the sensor structure and in fluid communication with theinline flow-cell chamber 2310 In the illustrated embodiment, thepressure equalization mechanism includes a pressure equalizationmembrane 2316 disposed between the inline flow-cell chamber 2310 and thereference solution chamber storing the reference solution 2334, althoughin other embodiments other pressure equalization mechanisms may be used.In FIG. 17E, the sensor structure 2300 is shown in a state in which thepressure within the inline flow-cell chamber is substantially higherthan the external pressure. When such a pressure differential exists,the membrane 2316 deforms outward as shown, increasing the volume of theinline flow-cell chamber to relieve the pressure differential. Byproviding a component of the sensor structure 2300 which can becomparatively readily deformable, pressure differential between theinline flow-cell chamber 2320 and the chamber comprising the referencesolution 2334 can be minimized or eliminated. In doing so, backflow ofthe process solution under pressure into the reference solution 2334 canbe prevented.

The pressure equalization mechanism may provide a volumetricdisplacement chosen based on a variety of factors. Depending on, forexample, the rigidity of the tubing or the rigidity of other componentsof the sensor structure 2300, the design of the pressure equalizationmechanism may be selected to provide a volumetric change under pressurewhich is greater if the tubing to which the sensor structure 2300 willbe attached is more rigid. If the tubing is more flexible, and canitself safely deform in response to increased pressure, a smaller amountof volumetric change may be provided by the pressure equalizationmechanism. The size of the pressure equalization mechanism, as well asthe flexibility of the pressure equalization mechanism, will affect theamount of volumetric change provided by the pressure equalizationmechanism when under pressure. In some embodiments, the pressureequalization mechanism may be designed to maintain the integrity of theinternal gaskets under a pressure differential of 70 psi, although otherembodiments may be designed with larger or smaller pressure differentialthresholds.

The amount of deformation induced in the pressure equalization membraneduring pressure equalization may be dependent not only on the pressuredifferential, but on the deformability of gaskets or other components ofthe sensor structure 2300 as well as the state of the reference solutionchamber storing the reference solution 2334, such as the amount of air,if any, within the chamber.

In addition to providing pressure compensation during use of the sensorstructure 2300, the pressure equalization membrane 2316 may alsocompensate for temperature variation in the reference solution 2334during storage of the sensor structure 2300, such that a pressuredifferential between the reference solution chamber storing thereference solution 2334 and the exterior of the sensor structure 2300can be reduced or eliminated during storage of the sensor structure2300.

It can also be seen in FIGS. 17D and 17E that, in contrast to theO-rings used in the illustrated embodiment of FIGS. 16A-16C, the sensorstructure 2300 includes alternative sealing structures in the form ofcup seals 2388 between the sensor drum 2320 and the facing internalsurface of the sensor structure 2300. In contrast to an O-ring, a cupseal can provide less frictional resistance to rotation of the sensordrum 2320 relative to the remainder of the sensor structure 2300,facilitating the movement of the sensor structure 2300 between the firstposition and the second position, while maintaining a seal. In otherembodiments, V-rings may be used in place of or in addition to suchO-rings or cup seals.

In some embodiments, some or all aspects of operation of the sensorstructures described herein may be automated. A connected instrument orother automation system may be placed in communication with the sensoror a mechanism coupled to the sensor in order to control the sensor.This communication may be a direct connection, or may utilize astandardized communications protocol, such as Ethernet or Modbus.

In some embodiments, an actuation mechanism may be connected to thesensor or included within the sensor to move or rotate a component ofthe sensor structure, such as a rotatable sensor drum, between a firstposition and a second position, and back to the first position. Theactuation mechanism may include a servo motor, stepper motor, or anyother suitable mechanism for causing movement of the sensor structurecomponent relative to other components of the sensor structure. In someembodiments, the actuation mechanism may be a distinct mechanism whichcan be mechanically coupled or connected to a lever or another componentof the sensor structure to move a component of the sensor structure.

In some embodiments, automation of the operation of some or all aspectsof the sensor structures described herein may allow installation andoperation without the need for subsequent or periodic user contact withthe sensor structure. Automation may also allow centralized control of aplurality of sensor structures, whether via an automation system, and/orremote user control.

In the foregoing description, specific details are given to provide athorough understanding of the examples. However, it will be understoodby one of ordinary skill in the art that the examples may be practicedwithout these specific details. Certain embodiments that are describedseparately herein can be combined in a single embodiment, and thefeatures described with reference to a given embodiment also can beimplemented in multiple embodiments separately or in any suitablesubcombination. In some examples, certain structures and techniques maybe shown in greater detail than other structures or techniques tofurther explain the examples.

The previous description of the disclosed embodiments is provided toenable any person skilled in the art to make or use the presentinvention. Various modifications to these embodiments will be readilyapparent to those skilled in the art, and the generic principles definedherein may be applied to other embodiments without departing from thespirit or scope of the invention. Thus, the present invention is notintended to be limited to the embodiments shown herein but is to beaccorded the widest scope consistent with the principles and novelfeatures disclosed herein.

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 29. A sensorstructure, comprising: a sensor housing; a inline flow chamberconfigured to allow a process medium to flow therethrough; a storagecompartment configured to retain a storage medium therein; a sensingelement retained at least partially within the sensor housing, thesensing element comprising a sensing surface, and rotatable relative tothe sensor housing to selectively place the sensing element in fluidcommunication with one of the inline flow chamber and the storagecompartment; and a sealing element circumscribing the storagecompartment and configured to engage a facing surface of the sensingelement to provide a seal inhibiting fluid flow out of the storagecompartment.
 30. The sensor structure of claim 29, additionallycomprising a pressure equalization mechanism in fluid communication withthe inline flow chamber;
 31. The sensor structure of claim 30, whereinthe pressure equalization mechanism comprises a portion of a wall of theinline flow chamber which is more readily deformable than the remainderof the wall of the inline flow chamber.
 32. The sensor structure ofclaim 30, wherein the pressure equalization mechanism allows the volumeof the inline flow chamber to increase in response to increased pressurewithin the inline flow chamber.
 33. The sensor structure of claim 30,wherein the pressure equalization mechanism comprises a deformablemembrane.
 34. The sensor structure of claim 29, additionally comprisinga reference chamber comprising reference solution for the sensingelement.
 35. The sensor structure of claim 34, additionally comprising aceramic wick extending between the reference chamber and the inline flowchamber.
 36. The sensor structure of claim 34, additionally comprising apressure equalization mechanism located between the inline flow chamberand the reference chamber.
 37. The sensor structure of claim 29, whereinthe sensing surface comprises a flat electrode substantially flush withthe facing surface of the sensing element.
 38. The sensor structure ofclaim 29, wherein each of the sensing surface, the inline flow chamber,and the storage compartment are located substantially the same radialdistance from an axis of rotation of the sensing element.
 39. The sensorstructure of claim 29, wherein rotating the sensing element between thefirst position and the second position does not displace a substantialamount of the storage solution from the storage compartment
 40. Thesensor structure of claim 29, wherein rotating the sensing elementbetween the first position and the second position does not expose theinterior of the storage compartment.
 41. The sensor structure of claim29, additionally comprising a movement detection mechanism configured todetect movement of the sensing element relative to the storagecompartment.
 42. The sensor structure of claim 41, wherein the movementdetection mechanism is configured to provide an indication of the timeat which the detected movement occurred.
 43. The sensor structure ofclaim 42, additionally comprising a memory chip configured to record atimestamp of movement of the sensing element relative to the storagecompartment.
 44. The sensor structure of claim 41, wherein the movementdetection mechanism comprises at least one of a proximity switch or amechanical contact.
 45. The sensor structure of claim 41, wherein themovement detection mechanism is configured such that the state of themovement detection mechanism can be detected by connectedinstrumentation, and the memory chip is configured to be written to bythe connected instrumentation.
 46. The sensor structure of claim 29,additionally comprising an actuation mechanism configured to rotate thesensing element relative to the sensor housing to selectively place thesensing element in fluid communication with one of the inline flowchamber and the storage compartment.
 47. A sensor structure, comprising:a sensor housing; a inline flow chamber configured to allow a processmedium to flow therethrough; a storage compartment configured to retaina storage medium therein; a sensing element retained at least partiallywithin the sensor housing, the sensing element comprising a sensingsurface, and rotatable relative to the sensor housing to selectivelyplace the sensing element in fluid communication with one of the inlineflow chamber and the storage compartment; an actuation mechanismconfigured to rotate the sensing element relative to the sensor housingto selectively place the sensing element in fluid communication with oneof the inline flow chamber and the storage compartment; and a sealingelement circumscribing the storage compartment and configured to engagea facing surface of the sensing element to provide a seal inhibitingfluid flow out of the storage compartment
 48. A sensor structure,comprising: a sensor housing; a inline flow chamber configured to allowa process medium to flow therethrough; a storage compartment configuredto retain a storage medium therein; a sensing element retained at leastpartially within the sensor housing, the sensing element comprising asensing surface, and rotatable relative to the sensor housing toselectively place the sensing element in fluid communication with one ofthe inline flow chamber and the storage compartment; a movementdetection mechanism configured to detect movement of the sensing elementrelative to the storage compartment; and a sealing elementcircumscribing the storage compartment and configured to engage a facingsurface of the sensing element to provide a seal inhibiting fluid flowout of the storage compartment